Stimulation of spermatogenesis with recombinant human follicle-stimulating hormone (follitropin alfa; GONAL-f): long-term treatment in azoospermic men with hypogonadotropic hypogonadism.
OBJECTIVE
To demonstrate the efficacy and safety of follitropin alfa administered with hCG on spermatogenesis in adult male hypogonadotropic hypogonadism (HH) patients.


METHODS
Phase III, multicenter, open-label, noncomparative.


METHODS
Seven US medical centers.


METHODS
A total of 36 adult males with severe HH.


METHODS
A total of 1,000 U hCG on alternate days for 3 to 6 months, with dose adjustments after 2 months, if necessary, to normalize T levels, followed by follitropin alfa 150 U and hCG on the same alternate days for 18 months, with dose adjustments as necessary.


METHODS
Proportion of patients with sperm density > or =1.5 x 10(6)/mL. Pubertal advancement and long-term safety and tolerability were also evaluated.


RESULTS
In total, 22 of 29 patients (75.9%) who received > or =1 dose of follitropin alfa and 20 of 25 patients (80%) who completed 18 months of hCG + follitropin alfa treatments achieved a sperm concentration > or =1.5 x 10(6)/mL. A sperm concentration >20 x 10(6)/mL was achieved by 8 of 29 men (27.5%). Median sperm concentration at 18 months was 5.2 x 10(6)/mL. Pubertal development continued during the study, and testis volumes increased. Five clinical pregnancies were achieved. Acne (52% of patients) was the most common side effect, and gynecomastia was reported in 10% of patients.


CONCLUSIONS
Long-term treatment of azoospermic HH men using follitropin alfa and hCG is effective for stimulating spermatogenesis and is well-tolerated.
Matsumoto
Alvin M
AM
Department of Medicine, University of Washington School of Medicine, Seattle, Washington; Geriatric Research, Education and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, Washington.
Snyder
Peter J
PJ
University of Pennsylvania, Philadelphia, Pennsylvania.
Bhasin
Shalender
S
Department of Medicine, Boston University, Boston, Massachusetts.
Martin
Kathryn
K
Reproductive Endocrinology, Massachusetts General Hospital, Boston, Massachusetts.
Weber
Thomas
T
Department of Medicine, Division of Endocrinology, Duke University Medical Center, Durham, North Carolina.
Winters
Stephen
S
Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Spratt
Daniel
D
Division of Reproductive Endocrinology and Infertility, Maine Medical Center and Maine Medical Center Research Institute, Portland, Maine.
Brentzel
Jim
J
Clinical Development, EMD Serono, Inc., Rockland, Massachusetts. Electronic address: jim.brentzel@emdserono.com.
O'Dea
Louis
L
Radius Health, Inc., Cambridge, Massachusetts.
D000293:Adolescent; D000328:Adult; D053713:Azoospermia / Q000188:drug therapy* / Q000473:pathology; D006063:Chorionic Gonadotropin / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D043373:Follicle Stimulating Hormone, Human / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D015292:Glycoprotein Hormones, alpha Subunit / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D007006:Hypogonadism / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D013081:Sperm Motility / Q000187:drug effects; D013091:Spermatogenesis / Q000187:drug effects*; D013094:Spermatozoa / Q000187:drug effects; D013737:Testis / Q000187:drug effects / Q000473:pathology; D013739:Testosterone / Q000097:blood; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
D006063:Chorionic Gonadotropin; D043373:Follicle Stimulating Hormone, Human; D015292:Glycoprotein Hormones, alpha Subunit; D013739:Testosterone